Lucy Emery, Alexa Hughes, Christiana Oji-Mmuo, Patricia Silveyra, Vincent P. R. Aluquin, Ann Donnelly, Roopa Siddaiah
Penn State Health College of Medicine and Penn State Health Children’s Hospital. Indiana University School of Medicine.
United States
Pediatric Research
Pediatr Res 2024;
DOI: 10.1038/s41390-024-03541-5
Abstract
Background: PDA and ASD are common intracardiac shunts noted in prematurely born infants. While there is evidence of persistent PDA and ASD associated with a higher risk for developing bronchopulmonary dysplasia (ICS-BPD) and pulmonary hypertension (ICS-BPD-PH), the underlying pathogenesis is poorly understood and hence challenging to identify at-risk infants. Our study goal was to evaluate transcriptomic expression and associated pathways in tracheal aspirates (TAs) of low-birth-weight infants with hemodynamically significant cardiac shunt (ICS) that develop bronchopulmonary dysplasia (ICS-BPD) and pulmonary hypertension (ICS-BPD-PH).
Methods: TAs were collected from preterm infants with ICS and a diagnosis of BPD or BPD-PH from a single center. 36 TA samples including 19 ICS-BPD and 17 ICS-BPD-PH were analyzed. MiRNA expression was determined via PCR arrays, and mRNA expression via RNA seq. Data were analyzed using limma.
Results: 11 miRNAs and 10 mRNAs were differentially expressed (adjusted p < 0.05) in ICS-BPD-PH group when compared to ICS-BPD. Ingenuity Pathway Analysis identified associations with cellular growth, proliferation, death, and cell function pathways.
Conclusion: TAs from preterm infants show differentially expressed miRNAs and mRNAs in ICS-BPD-PH when compared to ICS-BPD, an in-silico model identified target molecules that could be playing a role in BPD-PH pathogenesis in low-birth-weight infants with ICS.
Impact: Pulmonary hypertension associated with severe BPD (BPD-PH) is a distinct disease in preterm infants with severe BPD and the role of intracardiac shunt (ICS) in its development is controversial and often challenging for clinical management. Our pilot study, researching specific endotyping of infants with pulmonary hypertension associated with BPD using multiomics approach has identified molecular markers and potential underlying pathways associated with this condition. These markers could aid in stratifying high risk infants with ICS that are at risk for developing BPD-PH and aid clinical management.
Category
Class III. Pulmonary Hypertension Associated with Lung Disease
Acquired Patient Factors Associated with Pulmonary Vascular Disease
Potential Biomarkers Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes